The present invention relates to substituted 3-phenylpiperidine compounds, processes for their production, pharmaceutical compositions containing these compounds, as well as the use of these substances for the treatment or inhibition of various conditions, especially pain.
The treatment of chronic and non-chronic pain is of great importance in medicine. There is a universal need for highly effective pain therapies. The pressing need for a patient-friendly and target-oriented treatment of chronic and non-chronic pain, which is understood here to mean the successful and satisfactory treatment of pain for the patient, is documented in the large amount of scientific work that has recently appeared in the field of applied analgesics and in basic research on nociception.
Conventional opioids such as morphine are highly effective in the treatment of severe to extremely severe pain. Their use is restricted however on account of the known side effects, e.g. respiratory depression, vomiting, sedation, constipation and development of tolerance. Also, they are less effective in treating neuropathic or incidental pain, from which in particular patients with tumors suffer.
Among the opioids that are used in the treatment of pain, tramadol occupies a special position, since tramadol differs as regards its spectrum of side effects from conventional opioides (Analgesics—from Chemistry and Pharmacology to Clinical Application 228-230, Wiley 2002). Starting from tramadol it was now surprisingly found that the replacement of the cyclohexyldimethylamino group by a piperidine substituted on the nitrogen atom leads to substances effective in the treatment of pain.

Of the class of substituted 3-phenylpiperidine compounds, up to now only one derivative is known from the literature. WO 0039091 discloses 3-(3-methoxyphenyl)-1-(phenylmethyl)-3-piperidinol as an intermediate product formed in the synthesis of bisarylpiperidines. In this compound the piperidine nitrogen is provided with a benzyl protective group, though functionalisations of the benzyl group are not described. Also, U.S. Pat. No. 4,382,942 (=DE 3149703) mentions 3-(3-methoxyphenyl)-1-(phenylmethyl)-3-piperidinol as an intermediate product.